1. Date of download: 7/7/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Comparative Mortality Risk in Adult Patients With Schizophrenia, Depression, Bipolar Disorder, Anxiety Disorders, and Attention-Deficit/Hyperactivity Disorder Participating in Psychopharmacology Clinical Trials JAMA Psychiatry. 2013;70(10):1091-1099. doi:10.1001/jamapsychiatry.2013.149 Total Mortality and Suicide Rates per 100 000 Patient Exposure Years (PEY) From Clinical Trials Conducted During New Drug Approval Programs in AdultsTotal mortality and suicide risk (per 100 000 PEY) during acute and safety extension phases of clinical trials conducted to approve drugs for treatment of psychiatric disorders in adults. Data were obtained from US Food and Drug Administration Summary Basis of Approval reports with available PEY and corresponding mortality totals (see the Methods section for details). Anxiety disorder spectrum is inclusive of patients diagnosed with obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, generalized anxiety disorder, and social anxiety disorder. Error bars represent 95% confidence intervals for mortality and suicide rates (we could not estimate these for suicide rates in patients with anxiety owing to the limited number of observations). No deaths occurred among patients enrolled in adult clinical trials for attention-deficit/hyperactivity disorder (ADHD). Overall mortality rates differed significantly between patients on the basis of diagnosis (schizophrenia, bipolar disorder, depression, anxiety disorder, or ADHD) (χ 2 4 = 1760; P <.001). Post hoc analysis with Bonferroni correction for multiple comparisons revealed a significant difference in overall mortality rates between patients with schizophrenia, bipolar disorder, or depression (χ 2 2 = 32.4; P <.001). Figure Legend:

2. Date of download: 7/7/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Comparative Mortality Risk in Adult Patients With Schizophrenia, Depression, Bipolar Disorder, Anxiety Disorders, and Attention-Deficit/Hyperactivity Disorder Participating in Psychopharmacology Clinical Trials JAMA Psychiatry. 2013;70(10):1091-1099. doi:10.1001/jamapsychiatry.2013.149 Relationship Between Psychotropic Agents and Overall Mortality Risk Compared With Overall Mortality Risk With PlaceboOdds ratios were calculated by using mortality rates (per 100 000 patient exposure years) for patients assigned to active treatment or control arms based on mortality and exposure data from Food and Drug Administration Summary Basis of Approval reports. Mortality rates are not included for attention-deficit/hyperactivity disorder (ADHD) because no deaths occurred during the ADHD clinical trials. Atypical antipsychotic agents for schizophrenia included olanzapine, ziprasidone, risperidone, quetiapine, aripiprazole, asenapine, quetiapine sustained release, paliperidone, and iloperidone. Agents approved for bipolar disorder included atypical antipsychotic agents olanzapine, ziprasidone, risperidone, quetiapine, aripiprazole, and asenapine; mood stabilizers lithium carbonate, divalproex sodium, and carbamazepine; and combinations of atypical antipsychotic agents and mood stabilizers. Serotonergic antidepressants included selective serotonin reuptake inhibitors (SSRIs) (sertraline, paroxetine, paroxetine controlled release (CR), citalopram, and escitalopram), selective serotonin-norepinephrine reuptake inhibitors (SNRIs; venlafaxine, venlafaxine extended release (XR), duloxetine, and desvenlafaxine), and SSRIs plus nefazodone, trazodone, or vilazodone. Heterocyclic antidepressant agents included imipramine, amitryptiline, maprotiline, and mirtazapine. Anti-anxiety agents included fluoxetine, paroxetine, clonazepam, venlafaxine XR, and paroxetine CR. Figure Legend:

3. Date of download: 7/7/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Comparative Mortality Risk in Adult Patients With Schizophrenia, Depression, Bipolar Disorder, Anxiety Disorders, and Attention-Deficit/Hyperactivity Disorder Participating in Psychopharmacology Clinical Trials JAMA Psychiatry. 2013;70(10):1091-1099. doi:10.1001/jamapsychiatry.2013.149 Relationship Between Psychotropic Agents and Suicide Risk Compared With Suicide Risk With PlaceboOdds ratios were calculated by using suicide rates (per 100 000 patient exposure years) for patients assigned to active treatment or control arms based on suicide and exposure data from Food and Drug Administration Summary Basis of Approval reports. Suicide rates are not included for attention-deficit/hyperactivity disorder (ADHD) because no suicides occurred during the ADHD clinical trials. A suicide comparison is not included for bipolar disorders because no suicides occurred in placebo arms of bipolar disorder clinical trials (see Table 5 for details). Atypical antipsychotic agents for treatment of schizophrenia include olanzapine, ziprasidone, risperidone, quetiapine, aripiprazole, asenapine, quetiapine sustained release, paliperidone, and iloperidone. Serotonergic antidepressants included selective serotonin reuptake inhibitors (SSRIs) (sertraline, paroxetine, paroxetine CR (controlled release), citalopram, and escitalopram), selective serotonin-norepinephrine reuptake inhibitors (SNRIs; venlafaxine, venlafaxine extended release (XR), duloxetine, and desvenlafaxine, and SSRIs plus nefazodone, trazodone, or vilazodone. Heterocyclic antidepressant agents included imipramine, amitryptiline, maprotiline, and mirtazapine. Anti-anxiety agents included fluoxetine, paroxetine, clonazepam, venlafaxine XR, and paroxetine CR. Figure Legend: